Latest Issue

    Vol. 29 Issue 8 2023

      Original Article

    • QI Run-zhi,HE Shu-lin,LI Yue,ZHAO Yu-wei,GENG Liang,HE Jie,CHENG Meng-qi,HU Jia-qi,LI Cong-huang,HUA Bao-jin
      Vol. 29, Issue 8, Pages: 675-682(2023) DOI: 10.1007/s11655-022-3682-9
      Abstract:Objective:To investigate the efficacy of integrated Chinese and Western medicine extending the progression-free survival (PFS) and overall survival (OS) of limited-stage small-cell lung cancer (LS-SCLC) patients after the first-line chemoradiotherapy.Methods:The data of 67 LS-SCLC patients who received combined treatment of Chinese medicine (CM) and Western medicine (WM) between January 2013 and May 2020 at the outpatient clinic of Guang'anmen Hospital were retrospectively analyzed. Thirty-six LS-SCLC patients who received only WM treatment was used as the WM control group. The medical data of the two groups were statistically analyzed. Survival analysis was performed using the product-limit method (Kaplan–Meier analysis). The median OS and PFS were calculated, and survival curves were compared by the Log rank test. The cumulative survival rates at 1, 2, and 5 years were estimated by the life table analysis. Stratified survival analysis was performed between patients with different CM administration time.Results:The median PFS in the CM and WM combination treatment group and the WM group were 19 months (95% CI: 12.36–25.64) vs. 9 months (95% CI: 5.96–12.04), respectively, HR=0.43 (95% CI: 0.27–0.69, P < 0.001). The median OS in the CM and WM combination group and the WM group were 34.00 months (95% CI could not be calculated) vs. 18.63 months (95% CI: 16.43–20.84), respectively, HR=0.40 (95% CI: 0.24–0.66, P < 0.001). Similar results were obtained in the further stratified analysis of whether the duration of CM administration exceeded 18 and 24 months ( P < 0.001).Conclusion:The combination treatment of CM and WM with continuing oral administration of CM treatment after the first-line chemoradiotherapy for LS-SCLC patients produced better prognosis, lower risks of progression, and longer survival than the WM treatment alone. (Registration No. ChiCTR2200056616)  
      Keywords:limited-stage small cell lung cancer;combination of Chinese and Western medicine;overall survival;progression-free survival;Chinese medicine   
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      Published:2023-07-24
    • QIAN Xiao-li,Meng Di,LIU Heng,LIU Chao-he,ZHOU Ping,YANG Yin-he,WANG Jia-peng,XIAO Huai,DING Zhong-tao
      Vol. 29, Issue 8, Pages: 683-690(2023) DOI: 10.1007/s11655-023-3696-y
      Abstract:Objective:To explore the proliferation inhibitory effect of quinones from Blaps rynchopetera defense secretion on colorectal tumor cell lines.Methods:Human colorectal cancer cell HT-29, human colorectal adenocarcinoma cell Caco-2 and normal human colon epithelial cell CCD841 were chosen for the evaluation of inhibitory activity of the main quinones of B. rynchopetera defense secretion, including methyl p-benzoquinone (MBQ), ethyl p-benzoquinone (EBQ), and methyl hydroquinone (MHQ), through methyl thiazolyl tetrazolium assay. The tumor-related factors, cell cycles, related gene expressions and protein levels were detected by enzyme-linked immunosorbent assy, flow cytometry, RT-polymerase chain reaction and Western blot, respectively.Results:MBQ, EBQ, and MHQ could significantly inhibit the proliferation of Caco-2, with half maximal inhibitory concentration (IC 50 ) values of 7.04±0.88, 10.92±0.32, 9.35±0.83, HT-29, with IC 50 values of 14.90±2.71, 20.50±6.37, 13.90±1.30, and CCD841, with IC 50 values of 11.40±0.68, 7.02±0.44 and 7.83±0.05 μg/mL, respectively. Tested quinones can reduce the expression of tumor-related factors tumor necrosis factor α, interleukin (IL)-10, and IL-6 in HT-29 cells, selectively promote apoptosis, and regulate the cell cycle which can reduce the proportion of cells in the G 1 phase and increase the proportion of the S phase. Meanwhile, tested quinones could up-regulate mRNA and protein expression of GSK-3β and APC, while down-regulate that of β-catenin, Frizzled1, c-Myc, and CyclinD1 in the Wnt/β-catenin pathway of HT-29 cells.Conclusion:Quinones from B. rynchopetera defense secretion could inhibit the proliferation of colorectal tumor cells and reduce the expression of related factors, which would be functioned by regulating cell cycle, selectively promoting apoptosis, and affecting Wnt/β-catenin pathway-related mRNA and protein expressions.  
      Keywords:Blaps rynchopetera;Chinese medicine;quinones;anti-colorectal tumor;Wnt/β-catenin pathway   
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      Published:2023-07-24
    • WANG Ze-tai,PENG Yan,LOU Dan-dan,ZENG Si-ying,ZHU Yuan-chao,LI Ai-wu,LYU Ying,ZHU Dao-qi,FAN Qin
      Vol. 29, Issue 8, Pages: 691-698(2023) DOI: 10.1007/s11655-022-3689-2
      Abstract:Objective:To investigate the mechanism by which Chinese medicine Shengmai Yin (SMY) reverses epithelial-mesenchymal transition (EMT) through lipocalin-2 (LCN2) in nasopharyngeal carcinoma (NPC) cells CNE-2R.Methods:Morphological changes in EMT in CNE-2R cells were observed under a microscope, and the expressions of EMT markers were detected using quantitative real-time PCR (RT-qPCR) and Western blot assays. Through the Gene Expression Omnibus dataset and text mining, LCN2 was found to be highly related to radiation resistance and EMT in NPC. The expressions of LCN2 and EMT markers following SMY treatment (50 and 100 μg/mL) were detected by RT-qPCR and Western blot assays in vitro. Cell proliferation, migration, and invasion abilities were measured using colony formation, wound healing, and transwell invasion assays, respectively. The inhibitory effect of SMY in vivo was determined by observing a zebrafish xenograft model with a fluorescent label.Results:The CNE-2R cells showed EMT transition and high expression of LCN2, and the use of SMY (5, 10 and 20 μg/mL) reduced the expression of LCN2 and reversed the EMT in the CNE-2R cells. Compared to that of the CNE-2R group, the proliferation, migration, and invasion abilities of SMY high-concentration group were weakened ( P < 0.05). Moreover, SMY mediated tumor growth and metastasis in a dose-dependent manner in a zebrafish xenograft model, which was consistent with the in vitro results.Conclusions:SMY can reverse the EMT process of CNE-2R cells, which may be related to its inhibition of LCN2 expression. Therefore, LCN2 may be a potential diagnostic marker and therapeutic target in patients with NPC.  
      Keywords:epithelial-mesenchymal transition;lipocalin-2;nasopharyngeal carcinoma;radiation therapy;Shengmai Yin;Chinese medicine   
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      Published:2023-07-24
    • XU Ben,YUAN Chang-wei,ZHANG Jia-en
      Vol. 29, Issue 8, Pages: 699-706(2023) DOI: 10.1007/s11655-022-3690-9
      Abstract:Objective:To explore the effect of curcumin on the proliferation of renal cell carcinoma and analyze its regulation mechanism.Methods:In RCC cell lines of A498 and 786-O, the effects of curcumin (2.5, 5, 10 μmo/L) on the proliferation were analyzed by Annexin V+PI staining. Besides, A498 was inoculated into nude mice to establish tumorigenic models, and the model mice were treated with different concentrations of curcumin (100, 200, and 400 mg/kg), once daily for 30 days. Then the tumor diameter was measured, the tumor cells were observed by hematoxylin-eosin staining, and the protein expressions of miR-148 and ADAMTS18 were detected by immunohistochemistry. In vitro , after transfection of miR-148 mimics, miR-148 inhibitor or si-ADAMTS18 in cell lines, the expression of ADAMTS18 was examined by Western blotting and the cell survival rate was analyzed using MTT. Subsequently, Western blot analysis was again used to examine the autophagy phenomenon by measuring the relative expression level of LC3-Ⅱ/LC3-Ⅰ; autophagy-associated genes, including those of Beclin-1 and ATG5, were also examined when miR-148 was silenced in both cell lines with curcumin treatment.Results:Curcumin could inhibit the proliferation of RCC in cell lines and nude mice. The expressions of miR-148 and ADAMTS18 were upregulated after curcumin treatment both in vitroand in vivo ( P < 0.05). The cell survival rate was dramatically declined upon miR-148 or ADAMTS18 upregulated. However, si-ADAMTS18 treatment or miR-148 inhibitor reversed these results, that is, both of them promoted the cell survival rate.Conclusion:Curcumin can inhibit the proliferation of renal cell carcinoma by regulating the miR-148/ ADAMTS18 axis through the suppression of autophagy in vitroand in vivo. There may exist a positive feedback loop between miR-148 and ADAMTS18 gene in RCC.  
      Keywords:curcumin;renal cell carcinoma;MiR-148;ADAMTS18 gene;autophagy   
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      Published:2023-07-24
    • ZENG Juan-ni,TAN Jin-yu,MO Li
      Vol. 29, Issue 8, Pages: 707-713(2023) DOI: 10.1007/s11655-023-3698-9
      Abstract:Objective:To explore the therapeutic effect of naringin on colorectal cancer (CRC) and the related mechanism.Methods:Cell counting kit-8 (CCK-8) assay and annexin V-FITC/PI assay were used to detect the effect of naringin (50–400 μg/mL) on cell proliferation and apoptosis of CRC cells, respectively. The scratch wound assay and transwell migration assay were used to assess the effect of naringin on CRC cell migration. Four-week-old male nude mice were injected with HCT116 cells subcutaneously to establish the tumor xenograft model. Naringin was injected intraperitoneally at 50 mg/(kg•d), with solvent and 5-fluorouracil treatment as control. The width and length of the tumors were measured and recorded every 6 days, and tumor tissues were photographed and weighed on the last day of the 24-d observation period. Immunohistochemical staining for caspase-3, proliferating cell nuclear antigen and TUNEL assay were used to evaluate the effect of naringin on cell proliferation and apoptosis in tumor tissues. The body weight, food and water intake of mice were recorded, and the major organs in different treatment groups were weighed on the last day and stained with hematoxylin and eosin for histological analysis. Meanwhile, the routine blood indicators were recorded.Results:CCK-8 and annexin V-FITC/PI results confirmed that naringin (100, 200, and 400 μg/mL) could inhibit proliferation and promote apoptosis. The scratch wound assay and transwell migration assay results confirmed the inhibitory activity of naringin against CRC cells migration. In vivo results demonstrated the inhibitory effect of naringin on tumor growth with good bio-compatibility.Conclusion:Naringin inhibited colorectal carcinogenesis by inhibiting viability of CRC cells.  
      Keywords:apoptosis;colorectal cancer;migration;naringin;proliferation;tumor   
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      Published:2023-07-24
    • WANG Yun-hui,YU He,LIU Tie-gang,Teck Chuan Kong,ZHENG Zi-an,WAN Yu-xiang,BAI Chen,HAO Yu,MAO Ying-qiu,WU Jun,XU Jing-nan,CUI Li-jun,WANG Yu-han,SHAN Yan-ran,SHAN Yan-ran,GU Xiao-hong
      Vol. 29, Issue 8, Pages: 714-720(2023) DOI: 10.1007/s11655-023-3697-x
      Abstract:Objective:To investigate the effect of Yinlai Decoction (YD) on the microstructure of colon, and activity of D-lactic acid (DLA) and diamine oxidase (DAO) in serum of pneumonia mice model fed with high- calorie and high-protein diet (HCD).Methods:Sixty male Kunming mice were randomly divided into 6 groups by the random number table method: normal control, pneumonia, HCD, HCD with pneumonia (HCD-P), YD (229.2 mg/mL), and dexamethasone (15.63 mg/mL) groups, with 10 in each group. HCD mice were fed with 52% milk solution by gavage. Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water, twice daily, for 3 days. After hematoxylin-eosin staining, the changes in the colon structure were observed under light microscopy and transmission electron microscope, respectively. Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice.Results:The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact. The colonic mucosal goblet cells in the pneumonia group tended to increase, and the size of the microvilli varied. In the HCD-P group, the mucosal goblet cells showed a marked increase in size with increased secretory activity. Loose mucosal epithelial connections were also observed, as shown by widened intercellular gaps with short sparse microvilli. These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment, while there was no significant improvement after dexamethasone treatment. The serum DLA level was significantly higher in the pneumonia, HCD, and HCD-P groups as compared with the normal control group ( P < 0.05). Serum DLA was significantly lower in the YD group than HCD-P group ( P < 0.05). Moreover, serum DLA level significantly increased in the dexamethasone group as compared with the YD group ( P < 0.01). There was no statistical significance in the serum level of DAO among groups ( P > 0.05).Conclusions:YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure, thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice.  
      Keywords:Yinlai Decoction;Chinese medicine;pneumonia;microstructure;D-lactic acid;diamine oxidase   
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      Published:2023-07-24

      Acupuncture Research

    • XING Xi,JIANG Rong-lin,LEI Shu,ZHI Yi-hui,ZHU Mei-fei,HUANG Li-quan,HU Ma-hong,LU Jun,FANG Kun,WANG Qiu-yan
      Vol. 29, Issue 8, Pages: 721-729(2023) DOI: 10.1007/s11655-022-3670-0
      Abstract:Objective:To evaluate whether electroacupuncture (EA) would improve gastrointestinal function and clinical prognosis in patients with severe traumatic brain injury (TBI) complicocted by acute gastrointestinal injury (AGI).Methods:This multicenter, single-blind trial included patients with TBI and AGI admitted to 5 Chinese hospitals from September 2018 to December 2019. A total of 500 patients were randomized to the control or acupuncture groups using a random number table, 250 cases in each group. Patients in the control group received conventional treatment, including mannitol, nutritional support, epilepsy and infection prevention, and maintenance of water, electrolytes, and acid-base balance. While patients in the acupuncture group received EA intervention at bilateral Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), Tianshu (ST 25), and Zhongwan (RN 12) acupoints in addition to the conventional treatment, 30 min per time, twice daily, for 7 d. The primary endpoint was 28-d mortality. The secondary endpoints were serum levels of D-lactic acid (D-lac), diamine oxidase (DAO), lipopolysaccharide (LPS), motilin (MTL) and gastrin (GAS), intra-abdominal pressure (IAP), bowel sounds, abdominal circumference, AGI grade, scores of gastrointestinal failure (GIF), Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation (APACHE Ⅱ), Sequential Organ Failure Assessment (SOFA), and Multiple Organ Dysfunction Syndrome (MODS), mechanical ventilation time, intense care unit (ICU) stay, and the incidence of hospital-acquired pneumonia.Results:The 28-d mortality in the acupuncture group was lower than that in the control group (22.80% vs. 33.20%, P < 0.05). Compared with the control group, the acupuncture group at 7 d showed lower GIF, APACHE Ⅱ, SOFA, MODS scores, D-lac, DAO, LPS, IAP, and abdominal circumference and higher GCS score, MTL, GAS, and bowel sound frequency (all P < 0.05). In addition, the above indices showed simillar changes at 7 d compared with days 1 and 3 in the EA group (all P < 0.05).Conclusion:Early EA can improve gastrointestinal function and clinical prognosis in patients with severe TBI complicated by AGI. (Registration No. ChiCTR2000032276)  
      Keywords:electroacupuncture;traumatic brain injury;acute gastrointestinal injury;multicenter;randomized controlled trial   
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      Published:2023-07-24

      Literature Research

    • SHI Lan-jun,TIAN Zi-yu,HU Xiao-yi,XIU Wen-cui,JIAO Rui-min,HU Xiang-yu,Nicola Robinson,GANG Wei-juan,JING Xiang-hong
      Vol. 29, Issue 8, Pages: 730-737(2023) DOI: 10.1007/s11655-023-3691-3
      Abstract:Objective:To summarize and identify the available instruments/methods assessing the adequacy of acupuncture in randomized controlled trials (RCTs) for proposing a new improved instrument.Methods:A systematic literature search was carried out in 7 electronic databases from inception until 21st November 2022. Any study evaluating the adequacy or quality of acupuncture, specifying specific acupuncture treatment-related factors as criteria of subgroup analysis, or developing an instrument/tool to assess the adequacy or quality of acupuncture in an RCT was included. Basic information, characteristics and contents of acupuncture adequacy assessment were presented as frequencies and percentages.Results:Forty studies were included in this systematic review. Thirty-five studies (87.50%) were systematic reviews, none of which used formal methods to develop the assessment instruments/methods of acupuncture adequacy; of 5 methodological studies, only 1 study used a relatively formal method. Thirty-two studies (82.05%) assessed the components of acupuncture, while 7 (17.95%) assessed the overall quality of acupuncture. An independent assessment instrument/method was used to assess acupuncture adequacy in 29 studies (74.35%), whereas as one part of a methodological quality assessment scale in 10 (25.65%). Only 9 (23.00%) studies used the assessment results for subgroup analysis, sensitivity analysis or the criteria for inclusion in the meta-analysis.Conclusion:Assessment contents for adequacy or quality of acupuncture in RCTs hadn't still reached consensus and no widely used assessment tools appeared. The methodology of available assessment instruments/scales is far from formal and rigorous. A new instrument/tool assessing adequacy of acupuncture should be developed using a formal method.  
      Keywords:acupuncture;adequacy assessment;quality;randomized clinical trial;systematic review   
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      Published:2023-07-24

      Review

    • REN Qun-li,WANG Qian,ZHANG Xin-qun,WANG Miao,HU Huan,TANG Jun-jie,TANG Jun-jie,YANG Xiong-tong,RAN Ying-hui,LIU Huan-huan,SONG Zhi-xing,LIU Jian-guo,LI Xiao-lan
      Vol. 29, Issue 8, Pages: 738-749(2023) DOI: 10.1007/s11655-023-3693-1
      Abstract:Diosgenin, a steroidal sapogenin, obtained from Trigonella foenum-graecum, Dioscorea, and Rhizoma polgonati , has shown high potential and interest in the treatment of various cancers, such as oral squamous cell carcinoma, laryngeal cancer, esophageal cancer, liver cancer, gastric cancer, lung cancer, cervical cancer, prostate cancer, glioma, and leukemia. This article aims to provide an overview of the in vivo, in vitro, and clinical studies reporting the diosgenin's anticancer effects. Preclinical studies have shown promising effects of diosgenin on inhibiting tumor cell proliferation and growth, promoting apoptosis, inducing differentiation and autophagy, inhibiting tumor cell metastasis and invasion, blocking cell cycle, regulating immunity and improving gut microbiome. Clinical investigations have revealed clinical dosage and safety property of diosgenin. Furthermore, in order to improve the biological activity and bioavailability of diosgenin, this review focuses on the development of diosgenin nano drug carriers, combined drugs and the diosgenin derivatives. However, further designed trials are needed to unravel the diosgenin's deficiencies in clinical application.  
      Keywords:diosgenin;steroidal sapogenin;anticancer;molecular mechanism;biological activity   
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      Published:2023-07-24
    • SUN Hao-xian,ZHU Ying
      Vol. 29, Issue 8, Pages: 750-760(2023) DOI: 10.1007/s11655-023-3551-1
      Abstract:Ulcerative colitis (UC) is a chronic, non-specific intestinal disease that not only affects the quality of life of patients and their families but also increases the risk of colorectal cancer. The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome is an important component of inflammatory response system, and its activation induces an inflammatory cascade response that is involved in the development and progression of UC by releasing inflammatory cytokines, damaging intestinal epithelial cells, and disrupting the intestinal mucosal barrier. Chinese medicine (CM) plays a vital role in the prevention and treatment of UC and is able to regulate NLRP3 inflammasome. Many experimental studies on the regulation of NLRP3 inflammasome mediated by CM have been carried out, demonstrating that CM formulae with main effects of clearing heat, detoxifying toxicity, drying dampness, and activating blood circulation. Flavonoids and phenylpropanoids can effectively regulate NLRP3 inflammasome. Other active components of CM can interfere with the process of NLRP3 inflammasome assembly and activation, leading to a reduction in inflammation and UC symptoms. However, the reports are relatively scattered and lack systematic reviews. This paper reviews the latest findings regarding the NLRP3 inflammasome activation-related pathways associated with UC and the potential of CM in treating UC through modulation of NLRP3 inflammasome. The purpose of this review is to explore the possible pathological mechanisms of UC and suggest new directions for development of therapeutic tools.  
      Keywords:NLRP3 inflammasome;ulcerative colitis;Chinese medicine;mechanism of action;review   
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      Published:2023-07-24
    • ZHANG Ying,XIE Hui,HE Zhong-mei,ZHANG Feng,LI Ling-long,WANG Na,MAO De-hong
      Vol. 29, Issue 8, Pages: 761-768(2023) DOI: 10.1007/s11655-022-3678-5
      Abstract:The current review gives a comprehensive overview of the recent development in Chinese medicine (CM) for treating several kinds of acquired nerve deafness and tinnitus, as well as links the traditional principle to well-established pharmacological mechanisms for future research. To date, about 24 herbal species and 40 related ingredients used in CM to treat hearing loss and tinnitus are reported for the treatment of endocochlear potential, endolymph growth, lowering toxic and provocative substance aggregation, inhibiting sensory cell death, and retaining sensory transfer. However, there are a few herbal species that can be used for medicinal purposes. Nevertheless, clinical studies have been hampered by a limited population sample, a deficiency of a suitable control research group, or contradictory results. Enhanced cochlear blood flow, anti- inflammatory antioxidant, neuroprotective effects, and anti-apoptotic, as well as multi-target approach on different auditory sections of the inner ear, are all possible benefits of CM medications. There are numerous unknown natural products for aural ailment and tinnitus identified in CM that are expected to be examined in the future utilizing various aural ailment models and processes.  
      Keywords:aural ailment caused by noise;diabetic hearing impairment;presbycusis;ototoxicity;cochlear blood flow;review   
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